AbstractPurpose of reviewThe antiretroviral drugs, tenofovir and emtricitabine used as preexposure prophylaxis (PrEP), are also used in treatment of HIV. Drug resistance due to PrEP can therefore jeopardize future treatment options. This review discusses treatment of individuals that used PrEP in whom viral mutations against tenofovir (K65R) or emtricitabine (M184I/V) are found.Recent findingsAlthough no studies systematically investigated the optimal treatment of individuals who used PrEP before diagnosis, there is anecdotal evidence that HIV including the K65R and/or M184I/V can be successfully treated using recommended first-line regimens.SummaryDrug resistance can be ascribed to use of PrEP while having an unrecognized acute HIV infection, partial adherence to PrEP, and transmission of HIV resistant to PrEP drugs. First-line antiretroviral drug treatment in individuals who used PrEP before diagnosis must be optimized based on genotypic resistance test results. Individuals in whom M184I/V and/or K65R is detected can be treated with dolutegravir-based, bictegravir-based, or darunavir-based regimens plus tenofovir plus lamivudine or emtricitabine. Dual therapy using dolutegravir plus lamivudine is not recommended for induction therapy in individuals with viral mutations against the drugs used as PrEP. There is an urgent need to confirm the anecdotal evidence for successful treatment using first-line regimens.